This invention relates to the treatment of stroke.
Stroke occurs when a section of the brain becomes infarcted, with death of brain tissue following the interruption of cerebral blood supply. The cerebral infarcts associated with acute stroke cause sudden and dramatic neurological impairment. Stroke is the third most common cause of death in the adult population of the United States, and is a major cause of disability.
Although all body tissues are dependent upon oxygen delivered by the vasculature, the brain is so sensitive to oxygen deficit that brain cells die after only several minutes of ischemia, or impaired blood supply. Cerebral ischemia leading to stroke is caused predominantly by thrombosis, embolism or hemorrhage, with arterial blood flow blocked by blood clots, atherosclerotic plaque material, or other obstructions. The oxygen level drops in the brain tissue downstream from an occluded artery. With inadequate oxygenation, a cerebral infarct begins to form, made up of dead and dying brain tissue. Since central nervous tissue lacks the ability to regenerate, the functional capability contributed by the infarcted brain areas is permanently lost.
The infarct typically increases in size during the acute period after ischemia begins, as some of the "penumbra" tissue dies. The infarct penumbra refers to tissue which is affected by the oxygen deficit from the vessel blockage, but which receives enough oxygen from other blood vessels to maintain temporary viability. The ultimate size of the infarct, and the resultant extent of neural damage to the stroke patient, are influenced by several factors, which form the basis of medical therapy for acute stroke. Primary among these factors is the extent of vascular support for the endangered penumbra tissue.
Pharmacologic interventions have attempted to maximize the blood flow to stroke-affected brain areas which might yet be able to survive, but clinical effectiveness has proven elusive. As stated in Harrison's Principles of Internal Medicine (9th ed., 1980, p. 1926), "Despite experimental evidence that . . . [cerebral vasodilators] increase the cerebral blood flow, as measured by the nitrous oxide method, they have not proved beneficial in careful studies in human stroke cases at the stage of transient ischemic attacks, thrombosis-in-evolution, or in the established stroke. This is true of nicotinic acid, Priscoline, alcohol, papaverine, and inhalation of 5% carbon dioxide. . . . In opposition to the use of these methods is the suggestion that vasodilators are harmful rather than beneficial, since by lowering the systemic blood pressure they reduce the intracranial anastomotic flow, or by dilating blood vessels in the normal parts of the brain they steal blood from the infarct."